ac sympathetic imaging, which will greatly simplify innervation analysis. Registration URL https//www.clinicaltrials.gov; Unique identifier NCT01400334.
Regional denervation volume has superior cause-specific mortality prediction for SCA versus global parameters of sympathetic innervation. These results have widespread implications for future cardiac sympathetic imaging, which will greatly simplify innervation analysis. Registration URL https//www.clinicaltrials.gov; Unique identifier NCT01400334.Background Comprehensive hemodynamic impairment mapping using blood oxygenation-level dependent (BOLD) cerebrovascular reactivity (CVR) can be used to identify hemodynamically relevant symptomatic unilateral carotid artery disease. https://www.selleckchem.com/products/etc-1002.html Methods and Results This prospective cohort study was conducted between February 2015 and July 2020 at the Clinical Neuroscience Center of the University Hospital Zurich, Zurich, Switzerland. One hundred two patients with newly diagnosed symptomatic unilateral internal carotid artery (ICA) occlusion or with 70% to 99% ICA stenosis were included. An age-matched healthy cohort of 12 subjects underwent an identical BOLD functional magnetic resonance imaging examination. Using BOLD functional magnetic resonance imaging with a standardized CO2 stimulus, CVR impairment was evaluated. Moreover, embolic versus hemodynamic ischemic patterns were evaluated on diffusion-weighted imaging. Sixty-seven patients had unilateral ICA occlusion and 35 patients unilateral 70% to 99% ICA stenosis. Patients with ICA occlusion exhibited lower whole-brain and ipsilateral hemisphere mean BOLD-CVR values as compared with healthy subjects (0.12±0.08 versus 0.19±0.04, P=0.004 and 0.09±0.09 versus 0.18±0.04, P less then 0.001) and ICA stenosis cohort (0.12±0.08 versus 0.16±0.05, P=0.01 and 0.09±0.09 versus 0.15±0.05, P=0.01); however, only 40 (58%) patients of the cohort showed significant BOLD-CVR impairment. Conversely, there was no difference in mean BOLD-CVR values between healthy patients and patients with ICA stenosis, although 5 (14%) patients with ICA stenosis showed a significant BOLD-CVR impairment. No significant BOLD-CVR difference was discernible between patients with hemodynamic ischemic infarcts versus those with embolic infarct distribution (0.11±0.08 versus 0.13±0.06, P=0.12). Conclusions Comprehensive BOLD-CVR mapping allows for identification of hemodynamically relevant symptomatic unilateral carotid artery stenosis or occlusion.[Figure see text].[Figure see text].Background Metabolic remodeling precedes most alterations during cardiac hypertrophic growth under hemodynamic stress. The elevation of glucose utilization has been recognized as a hallmark of metabolic remodeling. However, its role in cardiac hypertrophic growth and heart failure in response to pressure overload remains to be fully illustrated. Here, we aimed to dissect the role of cardiac PKM1 (pyruvate kinase muscle isozyme 1) in glucose metabolic regulation and cardiac response under pressure overload. Methods Cardiac specific deletion of PKM1 was achieved by crossing the floxed PKM1 mouse model with the cardiomyocyte-specific Cre transgenic mouse. PKM1 transgenic mice were generated under the control of tetracycline response elements, and cardiac specific overexpression of PKM1 was induced by doxycycline administration in adult mice. Pressure overload was triggered by transverse aortic constriction (TAC). Primary neonatal rat ventricular myocytes were used to dissect molecular mechanisms. Moreover, metabolomics and NMR spectroscopy analyses were conducted to determine cardiac metabolic flux in response to pressure overload. Results We found that PKM1 expression is reduced in failing human and mouse hearts. Importantly, cardiomyocyte-specific deletion of PKM1 exacerbates cardiac dysfunction and fibrosis in response to pressure overload. Inducible overexpression of PKM1 in cardiomyocytes protects the heart against TAC-induced cardiomyopathy and heart failure. At the mechanistic level, PKM1 is required for the augmentation of glycolytic flux, mitochondrial respiration, and ATP production under pressure overload. Furthermore, deficiency of PKM1 causes a defect in cardiomyocyte growth and a decrease in pyruvate dehydrogenase complex activity at both in vitro and in vivo levels. Conclusions These findings suggest that PKM1 plays an essential role in maintaining a homeostatic response in the heart under hemodynamic stress.Background Although tobacco product use and transitions have been characterized in the general population, few studies have focused on individuals with established cardiovascular disease (CVD) in a population-based sample. Methods and Results We examined tobacco use prevalence and longitudinal patterns of tobacco product transitions in adults (?18 years) of the nationally representative PATH (Population Assessment of Tobacco and Health) study, from 2013 to 2014 (Wave 1) through 2016 to 2018 (Wave 4). Prevalent CVD was classified through self-report of having had a heart attack, heart failure, stroke, or other heart condition. Factors associated with tobacco product use and transitions were investigated using survey logistic regression. We examined 2615 participants with self-reported CVD at Wave 1. Overall, 28.9% reported current tobacco use, equating to ?6.2 million adults in the United States with prevalent CVD and current tobacco use. Among adults with CVD who are current tobacco users, the most commonly used product was cigarettes (82.8%), followed by any type of cigar (23.7%), and e-cigarette use (23.3%). E-cigarette use without concurrent cigarette use among participants with prevalent CVD was uncommon (1.1%). Factors associated with tobacco use were younger age, male sex, had lower education level, and lack of knowledge about the association between smoking and CVD. Men with prevalent CVD were less likely to use e-cigarettes compared with women (odds ratio [OR], 0.7; 95% CI, 0.5-0.9). Among cigarette users with CVD, transition rates between Waves 1 and 4 demonstrated less then 5% decrease in cigarette, with a 0.5% increase in e-cigarette use. Only ?10% were in formal tobacco cessation programs. Conclusions Despite known harmful cardiovascular effects, over one fourth of adults with prevalent CVD use tobacco products and few quit smoking over the 4 waves of the PATH data set.